Pavlenko Darya, Ishida Hirotake, Markan Anika, Akiyama Tasuku
Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, 1600 NW 10th Ave., RMSB2063, Miami, FL, USA.
Sci Rep. 2025 Jul 21;15(1):26432. doi: 10.1038/s41598-025-08612-z.
The parabrachial nucleus (PBN) plays a crucial role in transmitting itch and affective pain signals to the brain regions such as the central amygdala (CeA). While CGRP PBN neurons have been implicated in itch processing, the specific projections involved remain unclear. This study aimed to determine the proportion of itch-responsive PBN-CeA projections that express CGRP and to assess their functional role in itch and anxiety behaviors in mice. Using the Targeted Recombination in Active Populations system, we labeled itch-responsive PBN neurons with serotonin. Retrograde tracing revealed that approximately half of serotonin-responsive PBN neurons projecting to the CeA are CGRP. Optogenetic stimulation of these PBN-CeA neurons elicited scratching behavior but did not enhance pruritogen-induced scratching or affect anxiety-like behaviors. In a mouse model of chronic itch, the inhibition of PBN-CeA neurons significantly reduced spontaneous scratching without impacting anxiety-like behaviors. These findings suggest that serotonin-responsive PBN-CeA neurons include both CGRP and non-CGRP populations and selectively mediate itch signaling.
臂旁核(PBN)在将瘙痒和情感性疼痛信号传递至诸如中央杏仁核(CeA)等脑区的过程中发挥着关键作用。虽然降钙素基因相关肽(CGRP)阳性的PBN神经元已被证实与瘙痒处理有关,但其具体涉及的投射尚不清楚。本研究旨在确定表达CGRP的瘙痒反应性PBN-CeA投射的比例,并评估它们在小鼠瘙痒和焦虑行为中的功能作用。利用活性群体中的靶向重组系统,我们用血清素标记了瘙痒反应性PBN神经元。逆行追踪显示,投射到CeA的血清素反应性PBN神经元中约有一半是CGRP阳性的。对这些PBN-CeA神经元进行光遗传学刺激会引发抓挠行为,但不会增强致痒原诱导的抓挠,也不会影响焦虑样行为。在慢性瘙痒小鼠模型中,抑制PBN-CeA神经元可显著减少自发抓挠,而不影响焦虑样行为。这些发现表明,血清素反应性PBN-CeA神经元包括CGRP阳性和非CGRP阳性群体,并选择性地介导瘙痒信号。
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